Structural covariance network topology in individuals at clinical high risk for psychosis: the ENIGMA-CHR Study.

Recent stressful life events (SLE) are a risk factor for psychosis, but limited research has explored how SLEs affect individuals at clinical high risk (CHR) for psychosis. The current study investigated the longitudinal effects of SLEs on functioning and symptom severity in CHR individuals, where we hypothesized CHR would report more SLEs than healthy controls (HC), and SLEs would be associated with poorer outcomes. The study used longitudinal data from the EU-GEI High Risk study. Data from 331 CHR participants were analyzed to examine the effects of SLEs on changes in functioning, positive and negative symptoms over a 2-year follow-up. We compared the prevalence of SLEs between CHR and HCs, and between CHR who did (CHR-T) and did not (CHR-NT) transition to psychosis. CHR reported 1.44 more SLEs than HC (p < 0.001), but there was no difference in SLEs between CHR-T and CHR-NT at baseline. Recent SLEs were associated with poorer functioning and more severe positive and negative symptoms in CHR individuals (all p < 0.01) but did not reveal a significant interaction with time. CHR individuals who had experienced recent SLEs exhibited poorer functioning and more severe symptoms. However, as the interaction between SLEs and time was not significant, this suggests SLEs did not contribute to a worsening of symptoms and functioning over the study period. SLEs could be a key risk factor to becoming CHR for psychosis, however further work is required to inform when early intervention strategies mitigating against the effects of stress are most effective.

BackgroundStructural magnetic resonance imaging studies in individuals at clinical high risk (CHR) for psychosis have yielded conflicting results. MethodsThe aims of this study were to compare intracranial and structural brain volumes and variability of CHR individuals with those of healthy control (HC) subjects and to investigate brain volume differences and variability in CHR subjects with and without transition to psychosis. The PubMed and Embase databases were searched for relevant studies published before June 1, 2020. ResultsA total of 34 studies were deemed eligible, which included baseline data of 2111 CHR and 1472 HC participants. In addition, data were included for 401 CHR subjects who subsequently transitioned to psychosis and 1023 nontransitioned CHR participants. Whole-brain and left, right, and bilateral hippocampal volume were significantly smaller in CHR subjects than in HC subjects. Cerebrospinal fluid and lateral ventricle volumes were significantly larger in CHR subjects than in HC subjects. Variability was not significantly different in CHR subjects compared with HC subjects. CHR individuals with and without subsequent transition to psychosis did not show significant differences in any of the volumetric assessments or in variability. ConclusionsThis meta-analysis demonstrates reduced whole-brain and hippocampal volumes and increased cerebrospinal fluid and lateral ventricle volumes in CHR individuals. However, no significant differences were observed in any of the volumetric assessments between CHR individuals with and without subsequent transition to psychosis. These findings suggest that although structural brain alterations are present before the onset of the disorder, they may not significantly contribute to the identification of CHR individuals at the highest risk for the development of psychosis.

Individuals at clinical high risk (CHR) for psychosis exhibit altered facial emotion processing (FEP) and poor social functioning. It is unclear whether FEP deficits result from attentional biases, and further, how these abnormalities are linked to symptomatology (e.g., negative symptoms) and highly comorbid disorders that are also tied to abnormal FEP (e.g., depression). In the present study, we employed an eye-tracking paradigm to assess attentional biases and clinical interviews to examine differences between CHR (N = 34) individuals and healthy controls (HC; N = 46), as well as how such biases relate to symptoms and functioning in CHR individuals. Although no CHR-HC differences emerged in attentional biases, within the CHR group, symptoms and functioning were related to biases. Depressive symptoms were related to some free-view attention switching biases (e.g., to and from fearful faces, r = .50). Negative symptoms were related to more slowly disengaging from happy faces (r = .44), spending less time looking at neutral faces (r = - .42), and more time looking at no face (Avolition, r = .44). In addition, global social functioning was related to processes that overlapped with both depression and negative symptoms, including time looking at no face (r = - .68) and free-view attention switching with fearful faces (r = - .40). These findings are consistent with previous research, indicating that negative symptoms play a prominent role in the CHR syndrome, with distinct mechanisms relative to depression. Furthermore, the results suggest that attentional bias indices from eye-tracking paradigms may be predictive of social functioning.

Auditory and visual oddball stimulus processing deficits in clinical high risk for psychosis: Forecasting psychosis risk with N200 and P300.

Eveningness chronotype preference among individuals at clinical high risk for psychosis

Individuals can be classified as being at clinical high risk (CHR) for psychosis if they meet at least one of the ultra-high-risk (UHR) inclusion criteria (brief limited intermittent psychotic symptoms [BLIPS] and/or attenuated psychotic symptoms [APS] and/or genetic risk and deterioration syndrome [GRD]) and/or basic symptoms [BS]. The meta-analytical risk of psychosis of these different subgroups is still unknown. To compare the risk of psychosis in CHR individuals who met at least one of the major inclusion criteria and in individuals not at CHR for psychosis (CHR-). Electronic databases (Web of Science, MEDLINE, Scopus) were searched until June 18, 2015, along with investigation of citations of previous publications and a manual search of the reference lists of retrieved articles. We included original follow-up studies of CHR individuals who reported the risk of psychosis classified according to the presence of any BLIPS, APS and GRD, APS alone, GRD alone, BS, and CHR-. Independent extraction by multiple observers and random-effects meta-analysis of proportions. Moderators were tested with meta-regression analyses (Bonferroni corrected). Heterogeneity was assessed with the I2 index. Sensitivity analyses tested robustness of results. Publication biases were assessed with funnel plots and the Egger test. The proportion of each subgroup with any psychotic disorder at 6, 12, 24, 36, and 48 or more months of follow-up. Thirty-three independent studies comprising up to 4227 individuals were included. The meta-analytical proportion of individuals meeting each UHR subgroup at intake was: 0.85 APS (95%CI, 0.79-0.90), 0.1 BLIPS (95%CI, 0.06-0.14), and 0.05 GRD (95%CI, 0.03-0.07). There were no significant differences in psychosis risk at any time point between the APS and GRD and the APS-alone subgroups. There was a higher risk of psychosis in the any BLIPS greater than APS greater than GRD-alone subgroups at 24, 36, and 48 or more months of follow-up. There was no evidence that the GRD subgroup has a higher risk of psychosis than the CHR- subgroup. There were too few BS or BS and UHR studies to allow robust conclusions. There is meta-analytical evidence that BLIPS represents separate risk subgroup compared with the APS. The GRD subgroup is infrequent and not associated with an increased risk of psychosis. Future studies are advised to stratify their findings across these different subgroups. The CHR guidelines should be updated to reflect these differences.

The impact of COVID-19 pandemic on individuals at clinical high-risk for psychosis: Evidence from eye-tracking measures

Identifying functional network changing patterns in individuals at clinical high-risk for psychosis and patients with early illness schizophrenia: A group ICA study.

Preclinical and human data suggest that hippocampal dysfunction plays a critical role in the onset of psychosis. Neural hyperactivity in the hippocampus is thought to drive an increase in subcortical dopamine function through glutamatergic projections to the striatum. To examine the association between hippocampal glutamate levels in individuals at clinical high risk for psychosis and their subsequent clinical outcomes. This cross-sectional study of 86 individuals at clinical high risk for psychosis and 30 healthy control individuals, with a mean follow-up of 18.5 months, was conducted between November 1, 2011, and November 1, 2017, at early detection services in London and Cambridge, United Kingdom. Concentrations of glutamate and other metabolites were measured in the left hippocampus using 3-T proton magnetic resonance spectroscopy at the first clinical presentation. At follow-up, clinical outcomes were assessed in terms of transition or nontransition to psychosis using the Comprehensive Assessment of the At-Risk Mental State criteria and the level of overall functioning using the Global Assessment of Function scale. Of 116 total participants, 86 were at clinical high risk for psychosis (50 [58%] male; mean [SD] age, 22.4 [3.5] years) and 30 were healthy controls (14 [47%] male; mean [SD] age, 24.7 [3.8] years). At follow-up, 12 clinical high-risk individuals developed a first episode of psychosis whereas 74 clinical high-risk individuals did not; 19 clinical high-risk individuals showed good overall functioning (Global Assessment of Function ≥65), whereas 38 clinical high-risk individuals had a poor functional outcome (Global Assessment of Function <65). Compared with clinical high-risk individuals who did not become psychotic, clinical high-risk individuals who developed psychosis showed higher hippocampal glutamate levels (mean [SD], 8.33 [1.48] vs 9.16 [1.28] glutamate levels; P = .048). The clinical high-risk individuals who developed psychosis also had higher myo-inositol levels (mean [SD], 7.60 [1.23] vs 6.24 [1.36] myo-inositol levels; P = .002) and higher creatine levels (mean [SD], 8.18 [0.74] vs 7.32 [1.09] creatine levels; P = .01) compared with clinical high-risk individuals who did not become psychotic, and higher myo-inositol levels compared with healthy controls (mean [SD], 7.60 [1.23] vs 6.19 [1.51] myo-inositol levels; P = .005). Higher hippocampal glutamate levels in clinical high-risk individuals were also associated with a poor functional outcome (mean [SD], 8.83 [1.43] vs 7.76 [1.40] glutamate levels; P = .02). In the logistic regression analyses, hippocampal glutamate levels were significantly associated with clinical outcome in terms of transition and nontransition to psychosis (β = 0.48; odds ratio = 1.61; 95% CI, 1.00-2.59; P = .05) and overall functioning (β = 0.53; odds ratio = 1.71; 95% CI, 1.10-2.66; P = .02). The findings indicate that adverse clinical outcomes in individuals at clinical high risk for psychosis may be associated with an increase in baseline hippocampal glutamate levels, as well as an increase in myo-inositol and creatine levels. This conclusion suggests that these measures could contribute to the stratification of clinical high-risk individuals according to future clinical outcomes.

ObjectiveAlthough previous studies have reported impaired performance in the reading the mind in the eyes test (RMET), which measures complex emotion recognition abilities, in patients with schizophrenia, reports regarding individuals at clinical high risk (CHR) for psychosis have been inconsistent, mainly due to the interacting confounding effects of general cognitive abilities and age. We compared RMET performances across first-episode psychosis (FEP) patients, CHR individuals, and healthy controls (HCs) while controlling for the effects of both general cognitive abilities and age.MethodsA total of 25 FEP, 41 CHR, and 44 HC subjects matched for age participated in this study. RMET performance scores were compared across the groups using analysis of variance with sex and intelligence quotient as covariates. Exploratory Pearson’s correlation analyses were performed to reveal the potential relationships of RMET scores with clinical symptom severity in the FEP and CHR groups.ResultsRMET performance scores were significantly lower among FEP and CHR participants than among HCs. FEP patients and CHR subjects showed comparable RMET performance scores. RMET scores were negatively correlated with Positive and Negative Syndrome Scale (PANSS) positive symptom subscale scores in the FEP patients. No significant correlation was identified between RMET scores and other clinical scale scores.ConclusionImpaired RMET performance is present from the risk stage of psychosis, which might be related to positive symptom severity in early psychosis. Longitudinal studies are necessary to confirm the stability of complex emotion recognition impairments and their relationship with social functioning in early psychosis patients.

Cerebello-limbic functional connectivity patterns in youth at clinical high risk for psychosis

Individuals at clinical high risk (CHR) for psychosis often experience poor social functioning and impaired facial emotion recognition (FER); however, the impact of frequently comorbid symptoms upon these processes is underexplored. In particular, social anxiety is characteristic of this population and also related to poor social functioning and FER biases, such as misinterpreting neutral faces as negative or threatening; however, little is known about how social anxiety relates to these processes in CHR individuals. The present study examined the overlap of social anxiety, social functioning, and FER accuracy and bias. Participants (CHR N=62, healthy controls N=52) completed the self-report Social Interaction Anxiety Scale (SIAS), Penn Emotion Recognition-40 (ER-40) behavioural task, and interviewer-rated Global Functioning Scale-Social (GFS-S). The ER-40 was used to assess both FER accuracy (e.g., overall number of correct responses) and bias (e.g., mislabelling neutral faces as angry). Consistent with previous research, relative to controls, CHR participants had more social anxiety (d=-1.07), poorer social functioning (d=-1.62), and performed more poorly on the FER task (e.g., d=-.37). Within CHR participants, social anxiety was related to an anger detection bias (r=.28), above and beyond positive symptom severity, which in turn was related to FER accuracy (r=.26) and social functioning (r=-.28). These findings suggest that ongoing work examining social processes within CHR individuals needs to account for social anxiety and that social anxiety may be a useful preventive intervention target.

Neural structure and social dysfunction in individuals at clinical high risk for psychosis

Traditional measures for assessing functioning with adult patients with schizophrenia have been shown to be insufficient for assessing the issues that occur in adolescents and young adults at clinical high risk (CHR) for psychosis. The current study provides an expanded validation of the Global Functioning: Social (GF:Social) and Role (GF:Role) scales developed specifically for use with CHR individuals and explores the reliability and accuracy of the ratings, the validity of the scores in comparison to other established clinical measures, stability of functioning over a 2-year period, and psychosis predictive ability. Seven hundred fifty-five CHR individuals and 277 healthy control (HC) participants completed the GF:Social and Role scales at baseline as part of the North American Prodrome Longitudinal Study (NAPLS2). Inter-rater reliability and accuracy were high for both scales. Correlations between the GF scores and other established clinical measures demonstrated acceptable convergent and discriminant validity. In addition, GF:Social and Role scores were unrelated to positive symptoms. CHR participants showed large impairments in social and role functioning over 2-years, relative to the HCs, even after adjusting for age, IQ, and attenuated positive symptoms. Finally, social decline prior to baseline was more pronounced in CHR converters, relative to non-converters. The GF scales can be administered in a large-scale multi-site study with excellent inter-rater reliability and accuracy. CHR individuals showed social and role functioning impairments over time that were not confounded by positive symptom severity levels. The results of this study demonstrate that social decline is a particularly effective predictor of conversion outcome.

It has been suggested that resilience may be a protective factor with respect to mental illness. This may be an important factor for those who are vulnerable to psychiatric illness. Thus, the aims of this paper were to compare levels of resilience between individuals at clinical high risk (CHR) for psychosis and healthy controls, and to examine associations between resilience and clinical measures, functioning and trauma of CHR participants. Eighty participants, 40 CHR and 40 University of Calgary undergraduate students, completed two resilience questionnaires: the Connor-Davidson Resilience Scale and the Child and Youth Resilience Measure. A t-test revealed a significant difference between the groups on levels of resilience (t = 4.34, P < 0.01), demonstrating that CHR participants have lower levels of resilience than healthy controls. In terms of the associations between resilience and measures of mental health of CHR participants, it was found that higher levels of resilience were related to lower negative symptoms, depression and anxiety. Furthermore, resilient CHR participants showed higher levels of role functioning and generally reported higher positive schemas of self and others, as well as lower stress to reported life events. No associations were found between resilience and attenuated psychotic symptoms, social functioning, IQ and trauma. The results of the current study suggest that resilience may be beneficial to other mental issues present in CHR individuals but this may not be the case for attenuated psychotic symptoms.